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Molecular and Cellular Biology, October 2000, p. 7726-7734, Vol. 20, No. 20
Department of Biochemistry and Molecular
Biology, University of Kansas Medical Center, Kansas City, Kansas
66160-7421,1 and Department of
Pathology, University of Vermont College of Medicine, Burlington,
Vermont 05405-00682
Received 19 January 2000/Returned for modification 21 March
2000/Accepted 27 July 2000
The eukaryotic cell cycle is regulated by cyclin-dependent kinases
(CDKs). CDK4 and CDK6, which are activated by D-type cyclins during the
G1 phase of the cell cycle, are thought to be responsible for phosphorylation of the retinoblastoma gene product (pRb). The tumor suppressor p16INK4A inhibits phosphorylation of
pRb by CDK4 and CDK6 and can thereby block cell cycle progression
at the G1/S boundary. Phosphorylation of the
carboxyl-terminal domain (CTD) of the large subunit of RNA polymerase
II by general transcription factor TFIIH is believed to be an
important regulatory event in transcription. TFIIH contains a
CDK7 kinase subunit and phosphorylates the CTD. We have previously shown that p16INK4A inhibits phosphorylation of
the CTD by TFIIH. Here we report that the ability of
p16INK4A to inhibit CDK7-CTD kinase contributes
to the capacity to induce cell cycle arrest. These results
suggest that p16INK4A may regulate cell cycle
progression by inhibiting not only CDK4-pRb kinase activity but
also by modulating CDK7-CTD kinase activity. Regulation of
CDK7-CTD kinase activity by p16INK4A thus
may represent an alternative pathway for controlling cell cycle progression.
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Regulation of CDK7-Carboxyl-Terminal Domain Kinase Activity by
the Tumor Suppressor p16INK4A Contributes to Cell
Cycle Regulation
*
Corresponding author. Mailing address: Department of
Biochemistry and Molecular Biology, University of Kansas Medical
Center, 3901 Rainbow Blvd., Kansas City, KS 66160-7421. Phone: (913)
588-7033. Fax: (913) 588-7004. E-mail: hserizaw{at}kumc.edu.
Present address: Research and Development Division, Nippon Organon
K.K. 5-90, Miyakojima-ku, Osaka 534-0016, Japan.
Present address: Second Department of Medicine, Kurume University
School of Medicine, Kurume 830, Japan.
Molecular and Cellular Biology, October 2000, p. 7726-7734, Vol. 20, No. 20
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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